Effects of irradiation pretreatment on vascular endothelial cells in mice during hematopoietic stem cell transplantation

Abstract

Objective To explore the endothelial injury in mice with different doses of total body irradiation (TBI) for pre-treatment in hematopoietic stem cell transplantation (HSCT). Methods Six-eight-week-old female Balb/c mice were divided into three groups randomly: control group; lethal irradiation group (exposed to ~(60)Co 8.5 Gy in a single dose given at a rate of 0.53 Gy/min); reduced irradiation group (exposed to ~(60)Co 5.0 Gy in a single dose given at a rate of 0.53 Gy/min). The general state of the mice were observed, harvested peripheral white blood cells were counted and changes in endothelial cells (Ecs) and endothelial progenitor cells (EPCs) were examined by flow cytometry regularly. The morphologic changes of endothelia were observed under a light microscope and ultrastructure of tissue by a transmission electron microscope (TEM). Results In lethal irradiation group, circulating WBCs were less than 0.5×10~9/L at the day 3, while circulating Ecs increased and had a peak at the day 5, about 6.4 folds as that of control (P<0.05) and circulating EPCs reached the peak at the day 5, about 24.9 folds as that of control (P<0.05). Extensive parenchyma cells edema and few lymphocytes infiltration in the portal area of liver was found on the 5th day, but the ultrastructure of hepatic sinusoid Ecs showed that nuclear fragmentation, and nuclear chromatin gathered toward the margin and the endothelium integrity was destroyed. In reduced irradiation group, circulating WBCs started to decrease from the day 3 and to the lowest (0.8×10~9/L) at the day 7, and then recovered to the normal level gradually. Circulating Ecs, compared to lethal irradiation group, were increased and reached the peak latterly (increase: day 5 vs day 3, peak:day 7 vs dayS) and the amplitude was lower (P<0.05). Circulating EPCs were elevated earlier (day 1), but the amplitude was lower than the lethal irradiation group (P<0.05). The pathological changes and endothelium damage in the liver and small intestine were milder compared to lethal irradiation group. Conclusion Vascular endothelial injury occurs in the mice given total body irradiation, and the degree of injury correlates with the dose of irradiation. Key words: Transplantation conditioning; Whole-body irradiation; Endothelium,Vascular; Injury